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Article ; Online: COVID-19 vaccine effectiveness and evolving variants: understanding the immunological footprint.

Zaeck, Luca M / GeurtsvanKessel, Corine H / de Vries, Rory D

2023 Volume 11, Issue 5, Page(s) 395–396

MeSH term(s)	Humans ; COVID-19 Vaccines ; Vaccine Efficacy ; COVID-19/prevention & control
Chemical Substances	COVID-19 Vaccines
Language	English
Publishing date	2023-04-17
Publishing country	England
Document type	Journal Article ; Comment
ZDB-ID	2686754-0
ISSN	2213-2619 ; 2213-2600
ISSN (online)	2213-2619
ISSN	2213-2600
DOI	10.1016/S2213-2600(23)00140-6
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Zs.A 7041: Show issues

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Article ; Online: The implications of mpox breakthrough infections on future vaccination strategies.

Shamier, Marc C / Zaeck, Luca M / de Vries, Rory D / GeurtsvanKessel, Corine H

The Lancet. Infectious diseases

2023 Volume 24, Issue 1, Page(s) 6–8

MeSH term(s)	Humans ; Breakthrough Infections ; Mpox (monkeypox) ; Vaccination
Language	English
Publishing date	2023-09-04
Publishing country	United States
Document type	Journal Article
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(23)00518-2
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Zs.A 5743: Show issues

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Article ; Online: Chlamydia trachomatis

Jahnke, Rico / Matthiesen, Svea / Zaeck, Luca M / Finke, Stefan / Knittler, Michael R

Microbiology spectrum

2022 Volume 10, Issue 6, Page(s) e0281722

Abstract: Tunneling nanotubes (TNTs) are transient cellular connections that consist of dynamic membrane protrusions. They play an important role in cell-to-cell communication and mediate the intercellular exchanges of molecules and organelles. TNTs can form ... ...

Abstract	Tunneling nanotubes (TNTs) are transient cellular connections that consist of dynamic membrane protrusions. They play an important role in cell-to-cell communication and mediate the intercellular exchanges of molecules and organelles. TNTs can form between different cell types and may contribute to the spread of pathogens by serving as cytoplasmic corridors. We demonstrate that Chlamydia (
MeSH term(s)	Humans ; Chlamydia trachomatis ; HEK293 Cells ; Cell Communication ; Nanotubes/chemistry
Chemical Substances	Tunneling Nanotubes
Language	English
Publishing date	2022-10-11
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2807133-5
ISSN	2165-0497 ; 2165-0497
ISSN (online)	2165-0497
ISSN	2165-0497
DOI	10.1128/spectrum.02817-22
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Article ; Online: Analysis of Nipah Virus Replication and Host Proteome Response Patterns in Differentiated Porcine Airway Epithelial Cells Cultured at the Air-Liquid Interface.

Müller, Martin / Fischer, Kerstin / Woehnke, Elisabeth / Zaeck, Luca M / Prönnecke, Christoph / Knittler, Michael R / Karger, Axel / Diederich, Sandra / Finke, Stefan

Viruses

2023 Volume 15, Issue 4

Abstract: Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respiratory tract epithelia is scarce. Studies in non-differentiated ...

Abstract	Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respiratory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking in the determination of complex host response patterns in differentiated respiratory tract epithelia for the understanding of NiV replication and spread in swine. Here we characterized infection and spread of NiV in differentiated primary porcine bronchial epithelial cells (PBEC) cultivated at the air-liquid interface (ALI). After the initial infection of only a few apical cells, lateral spread for 12 days with epithelium disruption was observed without releasing substantial amounts of infectious virus from the apical or basal sides. Deep time course proteomics revealed pronounced upregulation of genes related to type I/II IFN, immunoproteasomal subunits, transporter associated with antigen processing (TAP)-mediated peptide transport, and major histocompatibility complex (MHC) I antigen presentation. Spliceosomal factors were downregulated. We propose a model in which NiV replication in PBEC is slowed by a potent and broad type I/II IFN host response with conversion from 26S proteasomes to immunoproteasomal antigen processing and improved MHC I presentation for adaptive immunity priming. NiV induced cytopathic effects could reflect the focal release of cell-associated NiV, which may contribute to efficient airborne viral spread between pigs.
MeSH term(s)	Animals ; Swine ; Nipah Virus/physiology ; Proteome/metabolism ; Epithelial Cells ; Virus Replication ; Respiratory Mucosa ; Cells, Cultured
Chemical Substances	Proteome
Language	English
Publishing date	2023-04-13
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v15040961
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Article ; Online: TGF-β/IFN-γ Antagonism in Subversion and Self-Defense of Phase II Coxiella burnetii

Matthiesen, Svea / Christiansen, Bahne / Jahnke, Rico / Zaeck, Luca M / Karger, Axel / Finke, Stefan / Franzke, Kati / Knittler, Michael R

Infection and immunity

2023 Volume 91, Issue 2, Page(s) e0032322

Abstract: Dendritic cells (DCs) belong to the first line of innate defense and come into early contact with invading pathogens, including the zoonotic bacterium Coxiella burnetii, the causative agent of Q fever. However, the pathogen-host cell interactions in C. ... ...

Abstract	Dendritic cells (DCs) belong to the first line of innate defense and come into early contact with invading pathogens, including the zoonotic bacterium Coxiella burnetii, the causative agent of Q fever. However, the pathogen-host cell interactions in C. burnetii-infected DCs, particularly the role of mechanisms of immune subversion beyond virulent phase I lipopolysaccharide (LPS), as well as the contribution of cellular self-defense strategies, are not understood. Using phase II Coxiella-infected DCs, we show that impairment of DC maturation and MHC I downregulation is caused by autocrine release and action of immunosuppressive transforming growth factor-β (TGF-β). Our study demonstrates that IFN-γ reverses TGF-β impairment of maturation/MHC I presentation in infected DCs and activates bacterial elimination, predominantly by inducing iNOS/NO. Induced NO synthesis strongly affects bacterial growth and infectivity. Moreover, our studies hint that Coxiella-infected DCs might be able to protect themselves from mitotoxic NO by switching from oxidative phosphorylation to glycolysis, thus ensuring survival in self-defense against C. burnetii. Our results provide new insights into DC subversion by Coxiella and the IFN-γ-mediated targeting of C. burnetii during early steps in the innate immune response.
MeSH term(s)	Humans ; Coxiella burnetii ; Transforming Growth Factor beta ; Q Fever/microbiology ; Interferon-gamma ; Dendritic Cells
Chemical Substances	Transforming Growth Factor beta ; Interferon-gamma (82115-62-6)
Language	English
Publishing date	2023-01-23
Publishing country	United States
Document type	Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218698-6
ISSN	1098-5522 ; 0019-9567
ISSN (online)	1098-5522
ISSN	0019-9567
DOI	10.1128/iai.00323-22
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Zs.A 684: Show issues

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Article ; Online: Innate Immune Signaling and Role of Glial Cells in Herpes Simplex Virus- and Rabies Virus-Induced Encephalitis.

Feige, Lena / Zaeck, Luca M / Sehl-Ewert, Julia / Finke, Stefan / Bourhy, Hervé

Viruses

2021 Volume 13, Issue 12

Abstract: The environment of the central nervous system (CNS) represents a double-edged sword in the context of viral infections. On the one hand, the infectious route for viral pathogens is restricted via neuroprotective barriers; on the other hand, viruses ... ...

Abstract	The environment of the central nervous system (CNS) represents a double-edged sword in the context of viral infections. On the one hand, the infectious route for viral pathogens is restricted via neuroprotective barriers; on the other hand, viruses benefit from the immunologically quiescent neural environment after CNS entry. Both the herpes simplex virus (HSV) and the rabies virus (RABV) bypass the neuroprotective blood-brain barrier (BBB) and successfully enter the CNS parenchyma via nerve endings. Despite the differences in the molecular nature of both viruses, each virus uses retrograde transport along peripheral nerves to reach the human CNS. Once inside the CNS parenchyma, HSV infection results in severe acute inflammation, necrosis, and hemorrhaging, while RABV preserves the intact neuronal network by inhibiting apoptosis and limiting inflammation. During RABV neuroinvasion, surveilling glial cells fail to generate a sufficient type I interferon (IFN) response, enabling RABV to replicate undetected, ultimately leading to its fatal outcome. To date, we do not fully understand the molecular mechanisms underlying the activation or suppression of the host inflammatory responses of surveilling glial cells, which present important pathways shaping viral pathogenesis and clinical outcome in viral encephalitis. Here, we compare the innate immune responses of glial cells in RABV- and HSV-infected CNS, highlighting different viral strategies of neuroprotection or Neuroinflamm. in the context of viral encephalitis.
MeSH term(s)	Animals ; Astrocytes/immunology ; Astrocytes/virology ; Blood-Brain Barrier/virology ; Central Nervous System/immunology ; Central Nervous System/virology ; Encephalitis, Viral/immunology ; Encephalitis, Viral/virology ; Herpes Simplex/immunology ; Herpes Simplex/virology ; Humans ; Immunity, Innate ; Inflammation ; Microglia/immunology ; Microglia/virology ; Neuroglia/immunology ; Neuroglia/virology ; Rabies/immunology ; Rabies/virology ; Rabies virus/immunology ; Signal Transduction ; Simplexvirus/immunology
Language	English
Publishing date	2021-11-25
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2516098-9
ISSN	1999-4915 ; 1999-4915
ISSN (online)	1999-4915
ISSN	1999-4915
DOI	10.3390/v13122364
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Article ; Online: Comparative pathogenesis of different phylogroup I bat lyssaviruses in a standardized mouse model.

Klein, Antonia / Eggerbauer, Elisa / Potratz, Madlin / Zaeck, Luca M / Calvelage, Sten / Finke, Stefan / Müller, Thomas / Freuling, Conrad M

PLoS neglected tropical diseases

2022 Volume 16, Issue 1, Page(s) e0009845

Abstract: A plethora of bat-associated lyssaviruses potentially capable of causing the fatal disease rabies are known today. Transmitted via infectious saliva, occasionally-reported spillover infections from bats to other mammals demonstrate the permeability of ... ...

Abstract	A plethora of bat-associated lyssaviruses potentially capable of causing the fatal disease rabies are known today. Transmitted via infectious saliva, occasionally-reported spillover infections from bats to other mammals demonstrate the permeability of the species-barrier and highlight the zoonotic potential of bat-related lyssaviruses. However, it is still unknown whether and, if so, to what extent, viruses from different lyssavirus species vary in their pathogenic potential. In order to characterize and systematically compare a broader group of lyssavirus isolates for their viral replication kinetics, pathogenicity, and virus release through saliva-associated virus shedding, we used a mouse infection model comprising a low (102 TCID50) and a high (105 TCID50) inoculation dose as well as three different inoculation routes (intramuscular, intranasal, intracranial). Clinical signs, incubation periods, and survival were investigated. Based on the latter two parameters, a novel pathogenicity matrix was introduced to classify lyssavirus isolates. Using a total of 13 isolates from ten different virus species, this pathogenicity index varied within and between virus species. Interestingly, Irkut virus (IRKV) and Bokeloh bat lyssavirus (BBLV) obtained higher pathogenicity scores (1.14 for IRKV and 1.06 for BBLV) compared to rabies virus (RABV) isolates ranging between 0.19 and 0.85. Also, clinical signs differed significantly between RABV and other bat lyssaviruses. Altogether, our findings suggest a high diversity among lyssavirus isolates concerning survival, incubation period, and clinical signs. Virus shedding significantly differed between RABVs and other lyssaviruses. Our results demonstrated that active shedding of infectious virus was exclusively associated with two RABV isolates (92% for RABV-DogA and 67% for RABV-Insectbat), thus providing a potential explanation as to why sustained spillovers are solely attributed to RABVs. Interestingly, 3D imaging of a selected panel of brain samples from bat-associated lyssaviruses demonstrated a significantly increased percentage of infected astrocytes in mice inoculated with IRKV (10.03%; SD±7.39) compared to RABV-Vampbat (2.23%; SD±2.4), and BBLV (0.78%; SD±1.51), while only individual infected cells were identified in mice infected with Duvenhage virus (DUVV). These results corroborate previous studies on RABV that suggest a role of astrocyte infection in the pathogenicity of lyssaviruses.
MeSH term(s)	Animals ; Astrocytes/virology ; Chiroptera/virology ; Genome, Viral ; Lyssavirus/genetics ; Lyssavirus/pathogenicity ; Mice ; Mice, Inbred BALB C ; RNA, Viral ; Random Allocation ; Rhabdoviridae Infections/pathology ; Rhabdoviridae Infections/virology ; Virus Cultivation ; Virus Replication ; Virus Shedding
Chemical Substances	RNA, Viral
Language	English
Publishing date	2022-01-18
Publishing country	United States
Document type	Journal Article
ZDB-ID	2429704-5
ISSN	1935-2735 ; 1935-2735
ISSN (online)	1935-2735
ISSN	1935-2735
DOI	10.1371/journal.pntd.0009845
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Article ; Online: Interaction of host cellular factor ANP32B with matrix proteins of different paramyxoviruses.

Günther, Maria / Bauer, Anja / Müller, Martin / Zaeck, Luca / Finke, Stefan

The Journal of general virology

2019 Volume 101, Issue 1, Page(s) 44–58

Abstract: ... proteins often exert host manipulatory functions in the nucleus. Matrix (M) proteins of henipaviruses and ... other paramyxoviruses shuttle through the nucleus, where host factors may bind for M modification or host-cell ... and Nipah virus M. Both accumulate in the nucleus in an ANP32B-dependent manner. Here we demonstrate ...

Abstract	Although most non-segmented negative-strand RNA viruses (NNSVs) replicate in the cytoplasm, NNSV proteins often exert host manipulatory functions in the nucleus. Matrix (M) proteins of henipaviruses and other paramyxoviruses shuttle through the nucleus, where host factors may bind for M modification or host-cell manipulation. Acidic leucine-rich nuclear phosphoprotein 32 family member B (ANP32B) is an interactor of Hendra and Nipah virus M. Both accumulate in the nucleus in an ANP32B-dependent manner. Here we demonstrate that the nuclear localization signal (NLS) of ANP32B is dispensable for HeV M binding. Specific purification of M-ANP32B but not of M-ANP32A complexes revealed that neither the negatively charged acidic nor the leucine-rich regions of ANP32 proteins per se mediate interactions with henipavirus M proteins. Whereas pneumovirus M did not interact with ANP32B, Newcastle disease virus (NDV, genus
MeSH term(s)	Active Transport, Cell Nucleus/physiology ; Cell Line ; Cell Nucleus/metabolism ; Cell Nucleus/virology ; Cytoplasm/metabolism ; HEK293 Cells ; Humans ; Nuclear Localization Signals/metabolism ; Nuclear Matrix-Associated Proteins/metabolism ; Nuclear Proteins/metabolism ; Paramyxovirinae/metabolism
Chemical Substances	ANP32B protein, human ; Nuclear Localization Signals ; Nuclear Matrix-Associated Proteins ; Nuclear Proteins
Language	English
Publishing date	2019-12-02
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	219316-4
ISSN	1465-2099 ; 0022-1317
ISSN (online)	1465-2099
ISSN	0022-1317
DOI	10.1099/jgv.0.001362
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Zs.A 610: Show issues

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Article ; Online: Analysis of Nipah Virus Replication and Host Proteome Response Patterns in Differentiated Porcine Airway Epithelial Cells Cultured at the Air–Liquid Interface

Müller, Martin / Fischer, Kerstin / Wöhnke, Elisabeth / Zaeck, Luca M. / Prönnecke, Christoph / Knittler, Michael R. / Karger, Axel / Diederich, Sandra / Finke, Stefan

2023

Abstract	Respiratory tract epithelium infection plays a primary role in Nipah virus (NiV) pathogenesis and transmission. Knowledge about infection dynamics and host responses to NiV infection in respiratory tract epithelia is scarce. Studies in non-differentiated primary respiratory tract cells or cell lines indicate insufficient interferon (IFN) responses. However, studies are lacking in the determination of complex host response patterns in differentiated respiratory tract epithelia for the understanding of NiV replication and spread in swine. Here we characterized infection and spread of NiV in differentiated primary porcine bronchial epithelial cells (PBEC) cultivated at the air–liquid interface (ALI). After the initial infection of only a few apical cells, lateral spread for 12 days with epithelium disruption was observed without releasing substantial amounts of infectious virus from the apical or basal sides. Deep time course proteomics revealed pronounced upregulation of genes related to type I/II IFN, immunoproteasomal subunits, transporter associated with antigen processing (TAP)-mediated peptide transport, and major histocompatibility complex (MHC) I antigen presentation. Spliceosomal factors were downregulated. We propose a model in which NiV replication in PBEC is slowed by a potent and broad type I/II IFN host response with conversion from 26S proteasomes to immunoproteasomal antigen processing and improved MHC I presentation for adaptive immunity priming. NiV induced cytopathic effects could reflect the focal release of cell-associated NiV, which may contribute to efficient airborne viral spread between pigs.
Keywords	Text ; ddc:570 ; Nipah virus -- air–liquid interface culture -- respiratory epithelium -- mass spectrometry -- immune response
Subject code	570
Language	English
Publishing date	2023-04-13
Publishing country	de
Document type	Article ; Online
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Article ; Online: Comparative pathogenesis of different phylogroup I bat lyssaviruses in a standardized mouse model.

Antonia Klein / Elisa Eggerbauer / Madlin Potratz / Luca M Zaeck / Sten Calvelage / Stefan Finke / Thomas Müller / Conrad M Freuling

PLoS Neglected Tropical Diseases, Vol 16, Iss 1, p e

2022 Volume 0009845

Abstract	A plethora of bat-associated lyssaviruses potentially capable of causing the fatal disease rabies are known today. Transmitted via infectious saliva, occasionally-reported spillover infections from bats to other mammals demonstrate the permeability of the species-barrier and highlight the zoonotic potential of bat-related lyssaviruses. However, it is still unknown whether and, if so, to what extent, viruses from different lyssavirus species vary in their pathogenic potential. In order to characterize and systematically compare a broader group of lyssavirus isolates for their viral replication kinetics, pathogenicity, and virus release through saliva-associated virus shedding, we used a mouse infection model comprising a low (102 TCID50) and a high (105 TCID50) inoculation dose as well as three different inoculation routes (intramuscular, intranasal, intracranial). Clinical signs, incubation periods, and survival were investigated. Based on the latter two parameters, a novel pathogenicity matrix was introduced to classify lyssavirus isolates. Using a total of 13 isolates from ten different virus species, this pathogenicity index varied within and between virus species. Interestingly, Irkut virus (IRKV) and Bokeloh bat lyssavirus (BBLV) obtained higher pathogenicity scores (1.14 for IRKV and 1.06 for BBLV) compared to rabies virus (RABV) isolates ranging between 0.19 and 0.85. Also, clinical signs differed significantly between RABV and other bat lyssaviruses. Altogether, our findings suggest a high diversity among lyssavirus isolates concerning survival, incubation period, and clinical signs. Virus shedding significantly differed between RABVs and other lyssaviruses. Our results demonstrated that active shedding of infectious virus was exclusively associated with two RABV isolates (92% for RABV-DogA and 67% for RABV-Insectbat), thus providing a potential explanation as to why sustained spillovers are solely attributed to RABVs. Interestingly, 3D imaging of a selected panel of brain samples from bat-associated ...
Keywords	Arctic medicine. Tropical medicine ; RC955-962 ; Public aspects of medicine ; RA1-1270
Subject code	616
Language	English
Publishing date	2022-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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